Heterogeneity in oligodendroglia: Is it relevant to mouse models and human disease?

There are many lines of evidence indicating that oligodendrocyte progenitor cells and oligodendrocyte populations in the central nervous system (CNS) are heterogeneous based on their developmental origins as well as from morphological and molecular criteria. Whether these distinctions reflect functional heterogeneity is less clear and has been the subject of considerable debate. Recent findings, particularly from knockout mouse models, have provided new evidence for regional variations in myelination phenotypes, particularly between brain and spinal cord. These data raise the possibility that oligodendrocytes in these regions have different functional capacities and/or ability to compensate for loss of a specific gene. The goal of this review is to briefly revisit the evidence for oligodendrocyte heterogeneity and then to present data from transgenic and demyelinating mouse models suggesting functional heterogeneity in myelination, demyelination, and remyelination in the CNS and, finally, to discuss the implications of these findings for human diseases.